ABSTRACT The toxicological significance of different kinds of minor alterations in the axial skeleton of foetal rat is still a matter of debate. These changes can be better evaluated by means of the double staining technique for cartilage and calcified tissue, which helps to distinguish between deficient calcification and actual structural changes. Sternebral alterations are a frequent finding in prenatal toxicity studies, while in hu- mans they are seldom observed. However, very few data exist for the rat with regard to their persistence and/or consequences in postnatal life. Abnormalities of the vertebral bodies might be functionally important, but comparatively little attention has been given to them in prenatal toxicology. By contrast, the little significance of wavy ribs, potentially reversible alterations, has been extensively studied. The transiency of extra ribs in the rat might be a species-specific feature, but they have been reported to cause health problems in humans. It is important to recognize a dose-dependent trend both for specific minor changes and for general parameters (e.g., sternebral alterations). Finally, the range of prevalences in historical controls may be an insensitive parameter, due to the wide variability between different control groups. This range could be better replaced by the average prevalence ? Standard Deviation.
ABSTRACT The relationship between ethylenethiourea (ETU)-induced malformations of cultured rat whole embryos and the alterations of midbrain (MB) cells was investigated and species-specific ETU-induced alterations between rat and mouse MB cells were determined. Herefore, we developed new methods for monitoring teratogenic activities in serum fluids without heat treatment. The serum samples were prepared from rats and mice given ETU, and ETU-teratogenicity was evaluated in both species. We determined that the different sensitivity of the midbrain of the rat and mouse may be the main reason that ETU was teratogenic in rats but not in mice. Next, we showed that MB-cultures are unsuitable for estimating the teratogenic potential of arotinoids. MB differentiation was adversely affected only at concentrations which caused cell death. Finally, we demonstrated that the embryolethal action of new herbicides is not detectable in the micromass teratogenic test. However, the V79 colony assay may be useful for preliminary screening of embryolethal effects of herbicides.
ABSTRACT The search for a carnivore as an addition to a multilevel test system for determining developmental toxicity has been extended to include the ferret. The follow- ing discussion is an effort to simplify the procedures which should be used with this species when conducting a typical Segment I1 - Teratology Study and to reduce the un- certainties which always accompany the introduction of a different animal model. It is recommended that developmental toxicity studies in ferrets include a positive control group. All-trans retinoic acid (15 mg/kg on day 14 of gestation) had minimal effects on the dam and her pregnancy and maximal effects on the fetus. Administration of retinoic acid did not alter maternal weight or weight gain nor affect the average num- bers of corpora lutea, implantations, resorptions or litter sizes. It did, however, reduce fetal body weight, produce gross external alterations in 90.6% of the fetuses and in- crease the skeletal alterations (particularly of the skull) in the exposed fetuses as com- pared with controls. Timed pregnant ferrets may be received from a supplier within a day or two after mating without interfering with implantation which occurs on day 12. Intubation with the test article is conducted throughout organogenesis from day 12 to day 30 with sacrifice on day 35 of gestation. Examination of the ferret fetuses is similar to that conducted with rat fetuses.
ABSTRACT Eighteen cases of anencephalic fetuses were examined to explore the ab- normal growth of the tongue papillae. All 18 cases consistently showed severe hypopla- sia of the tongue papillae and taste buds. The filiform papillae showed the most severe hypoplasia. Both epithelial ingrowth and crypt formation of the tongue papillae were retarded from as early as gestational age 19-20 weeks, thus the filiform papillae be- came greatly arrested showing smooth surfaced and thick keratinized epithelium. The fungiform papillae decreased in number and were of abnormal size. The direction of the papillae was occasionally reversed. The taste bud of the fungiform papillae was markedly hypoplastic and was often missing. Meanwhile the vallate papillae were relatively well developed although frequently abnormal in shape. The distribution of the taste bud was irregular, and several taste buds were observed on the top of the vallate papillae. The taste buds were generally hypoplastic, and some of them showed degenerative or cystic change. In conclusion the tongue papillae, indicative of a highly proliferative epithelium, seem to be definitely affected by the generalized growth retardation in anencephalics.
ABSTRACT Data collected in our institution, in which approximately one-fourth of the prenatal diagnoses for inborn errors of metabolism in Japan are performed, suggest somewhat higher prevalences of Gaucher disease and mucolipidoses in Japan than in the United States, European countries and Australia. Hunter disease seems to be more frequent than Hurler disease in Japan while the reverse is true in Europe and Australia. In contrast, family histories of Pompe disease or cystinosis were much less frequent indications for prenatal diagnosis in Japanese than in Caucasian populations. The results of a recent multicenter survey conducted in Japan on the indications for and reliability of prenatal diagnoses for inherited metabolic disease support the conclusions drown from our data. The relative frequencies of each of the lysosomal storage diseases, with the exception of the mucopolysaccharidoses, obtained from our prenatal diagnosis surveys were quite similar to those derived from an epidemiological study of lysosomal storage diseases in Japan. We conclude that prenatal diagnosis can be used an indicator of the prevalences of lysosomal storage diseases in Japan.
ABSTRACT Pregnant Wistar rats were given a single i. p. injection of 30 mg/kg methylazoxymethanol (MAM) acetate or saline on day 13 of pregnanty (vaginal plug = day 0). All offspring were subjected to reflex tests during the preweaning period (sur- face righting reflex, from 3 to 12 days of age; negative geotaxis reflex, from 5 to 12 days of age), and then selected male rats were subjected to open-field test during the postweaning period (from 21 to 35 days of age). The MAM-treated rats showed significantly longer latencies in the both reflex tests, and also significant hyperactivity in the open-field test. These behavioral alterations were analyzed in relation to the large size reduction in the cerebral cortex and the morphological abnormalities of the hippocampus in the MAM-treated rats.